Binodenoson
(Synonyms: 比诺地松,MRE-0470; WRC 0470) 目录号 : GC64647
Binodenoson (MRE-0470) 是一种有效且选择性 A2A 腺苷受体激动剂(KD=270 nM)。Binodenoson 是一种短效冠状动脉扩张剂，作为放射性示踪剂的辅助物，用于心肌负荷显像。
Cas No.:144348-08-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Binodenoson (MRE-0470) is a potent and selective A2A adenosine receptor agonist (KD=270 nM). Binodenoson is being developed as a short-acting coronary vasodilator as an adjunct to radiotracers for use in myocardial stress imaging[1].
Binodenoson (MRE-0470) (30-300 nM) decreases oxidative activity of tumor necrosis factor-α-primed FMLP-stimulated polymorphonuclear leukocytes in human whole blood and acts synergistically with Rolipram[1].
Binodenoson (infused 0-0.9 μg/kg/h; adult Wistar rat; rat bacterial meningitis model), with or without rolipram (0-0.01 μg/kg/h), inhibits pleocytosis and reduces the lipopolysaccharide-induced increase in blood-brain barrier permeability (BBBP), indicative of decreased neutrophil-induced damage[1].
[1]. Sullivan GW, et al. Neutrophil A2A adenosine receptor inhibits inflammation in a rat model of meningitis: synergy with the type IV phosphodiesterase inhibitor, rolipram. J Infect Dis. 1999;180(5):1550-1560.
[2]. Glover DK, et al. Pharmacological stress thallium scintigraphy with 2-cyclohexylmethylidenehydrazinoadenosine (WRC-0470). A novel, short-acting adenosine A2A receptor agonist. Circulation. 1996;94(7):1726-1732.
| Cas No. | 144348-08-3 | SDF | Download SDF |
| 别名 | 比诺地松,MRE-0470; WRC 0470 | ||
| 分子式 | C17H25N7O4 | 分子量 | 391.42 |
| 溶解度 | DMSO : 125 mg/mL (319.35 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5548 mL | 12.774 mL | 25.548 mL |
| 5 mM | 0.511 mL | 2.5548 mL | 5.1096 mL |
| 10 mM | 0.2555 mL | 1.2774 mL | 2.5548 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Safety of Binodenoson, a selective adenosine A2A receptor agonist vasodilator pharmacological stress agent, in healthy subjects with mild intermittent asthma
Circ Cardiovasc Imaging 2009 Nov;2(6):492-8.PMID:19920048DOI:10.1161/CIRCIMAGING.108.817932.
Background: The pharmacological stress agents adenosine and dipyridamole are contraindicated in asthma patients because of the risk of adenosine receptor-mediated bronchospasm. Binodenoson, a selective adenosine A(2A) receptor agonist, produces maximal coronary hyperemia during pharmacological stress testing yet has a low affinity for the adenosine A(1), A(2B), and A(3) receptors that are probably responsible for bronchospasm. This study was conducted to assess the safety of Binodenoson in 87 healthy young adult volunteers with documented mild, intermittent asthma. Methods and results: This study consisted of a dose-escalating, single-blinded phase and a placebo-controlled, double-blinded phase conducted in healthy, young adults with documented mild, intermittent, asthma. In the single-blinded phase, 3 sequential cohorts of 8 subjects received intravenous Binodenoson (0.5, 1.0, and 1.5 microg/kg). In the double-blinded phase, commenced after medical review of results from the single-blinded phase, subjects were randomly assigned 2:1 to either Binodenoson 1.5 microg/kg (n=41) or placebo (n=22). The primary end point was clinically significant bronchoconstriction, defined as a decrease in forced expiratory volume in 1 second of >/=20% from the preinjection measure. Secondary safety end points were changes from preinjection measure in forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow during the middle 50% of the forced vital capacity; vital signs; pulse oximetry; and adverse events. Binodenoson caused no clinically significant bronchoconstriction or alterations in pulmonary function parameters and transiently increased heart rate and systolic blood pressure. The most common treatment-emergent adverse events were tachycardia, dizziness, and flushing. Conclusions: Binodenoson was safe, well tolerated, and caused no clinically significant bronchoconstriction or pulmonary responses in a small population of healthy subjects with mild, intermittent asthma.
Coronary circulation responses to Binodenoson, a selective adenosine A2A receptor agonist
Am J Cardiol 2007 Jun 1;99(11):1507-12.PMID:17531571DOI:10.1016/j.amjcard.2006.12.086.
The purpose of this study was to define Binodenoson dosing regimens that produce coronary hyperemia comparable to those of adenosine and that are tolerated well by patients. An open-label, randomized, parallel-group, multicenter study enrolled adult patients who had completed diagnostic cardiac catheterization. Coronary blood flow velocity (CBFV) was measured with a Doppler flow wire, and CBFV reserve was determined before Binodenoson administration. Patients (n = 133) received a 3-minute infusion of 0.3, 0.5, or 1 microg/kg/min or a bolus intravenous injection of 1.5 or 3 microg/kg. Coronary hyperemic responses were evident within seconds of administering Binodenoson, and the magnitudes and durations of coronary hyperemic responses were dose related. The 1.5- and 3-microg/kg doses, by infusion or bolus, produced maximal coronary hyperemia equivalent to CBFV reserve. All doses transiently decrease blood pressure and increased heart rate and rate-pressure product. In conclusion, the 1.5-microg/kg Binodenoson bolus dose produced nearly maximal coronary hyperemia by 4.5 +/- 3.7 minutes that was sustained for 7.4 +/- 6.86 minutes, was accompanied by modest changes in blood pressure, heart rate, and rate-pressure product, and produced no adverse changes on electrocardiogram, including no second- or third-degree atrioventricular block.
Pharmacokinetics and safety of Binodenoson after intravenous dose escalation in healthy volunteers
J Nucl Cardiol 2005 Mar-Apr;12(2):166-71.PMID:15812370DOI:10.1016/j.nuclcard.2004.12.294.
Background: Binodenoson, a highly selective agonist of the adenosine A 2A receptor, is being developed as a short-acting coronary vasodilator as an adjunct to radiotracers for use in myocardial stress imaging. This study was designed to assess the single-dose pharmacokinetics, safety, and tolerability of intravenous Binodenoson. Methods and results: This was a single-center, open-label, nonrandomized, dose-escalation study in 24 healthy volunteers. Each subject received 3 successive intravenous doses of Binodenoson (0.1, 0.2, 0.4, 0.6, 1, 2, 3, 4, 5, and 6 microg/kg), each infused over a period of 10 minutes and separated by washout periods of at least 120 minutes. Generally, Binodenoson was well tolerated. There were no serious adverse events. However, there was a dose-related increase in adverse events (e.g., headache, nausea, vasodilation, chest pain), consistent with the pharmacology of the drug. Binodenoson exhibited linear pharmacokinetics as indicated by a dose-proportional increase in peak concentration (C max ) and area under the concentration-time curve (AUC). Systemic clearance was independent of dose but was correlated with body weight. The mean terminal half-life of Binodenoson across all doses was 10 +/- 4 minutes. Conclusions: Overall, Binodenoson was well tolerated and exhibited linear pharmacokinetics when administered intravenously over a 60-fold dose range from 0.1 to 6 microg/kg.
Gateways to clinical trials
Methods Find Exp Clin Pharmacol 2004 May;26(4):295-318.PMID:15319808doi
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 166Ho-DOTMP 5A8; A-179578, abetimus sodium, adefovir dipivoxil, AGI-1067, AIDSVAX gp120 B/B, AK-602, alefacept alemtuzumab, aliskiren fumarate, ALVAC vCP1433, ALVAC vCP1452, anecortave acetate, arzoxifene hydrochloride, atazanavir sulfate, atlizumab, avasimibe; Binodenoson, BMS-488043; Choriogonadotropin alfa, ciclesonide, COL-1621, CVT-3146, CVT-E002, Cypher; Daptomycin, darbepoetin alfa, darunavir, D-D4FC, deferasirox, desloratadine, desmoteplase, duloxetine hydrochloride, DX-9065a; E-5564, efalizumab, emfilermin, emivirine, emtricitabine, enfuvirtide, estradiol acetate, ezetimibe; Frovatriptan; Gallium maltolate, gefitinib; HIV-1 Immunogen, human insulin; Iguratimod, IL-4/IL-13 Trap, imatinib mesylate, inhaled insulin, insulin glargine, irofulven, ISS-1018, ivabradine hydrochloride; Lutropin alfa; Melatonin; Nesiritide; O6-Benzylguanine, omapatrilat, oritavancin, ospemifene; Parecoxib sodium, peginterferon alfa-2a, pexelizumab, pimecrolimus, pirfenidone, pramlintide acetate, prasterone sulfate PT-141; Rasburicase, razaxaban hydrochloride, recombinant malaria vaccine, rhBMP-2/ACS, roflumilast, rosiglitazone maleate/metformin hydrochloride, rotavirus vaccine; SCH-D, sitaxsentan sodium, solifenacin succinate; Targinine hydrochloride, taxus, TER-199, tramadol hydrochloride/acetaminophen; Valdecoxib, valganciclovir hydrochloride, vatalanib succinate, VEG Trap(R1R2); Ximelagatran; Yttrium Y90 Epratuzumab.
Randomized, controlled dose-ranging study of the selective adenosine A2A receptor agonist Binodenoson for pharmacological stress as an adjunct to myocardial perfusion imaging
Circulation 2004 Feb 3;109(4):457-64.PMID:14734517DOI:10.1161/01.CIR.0000114523.03312.7D.
Background: Dipyridamole and adenosine cause frequent side effects as a result of nonspecific adenosine receptor stimulation. Selective agonism of the adenosine A2A receptor should result in a similar degree of coronary vasodilation (and thus similar perfusion images) with fewer side effects. Methods and results: In a multicenter, randomized, single-blind, 2-arm crossover trial, 240 patients underwent 2 single photon emission computed tomographic (SPECT) imaging studies in random order, first after pharmacological stress with adenosine and a second study with the selective adenosine A2A receptor agonist Binodenoson, using 1 of 4 dosing regimens. Safety, tolerability, and SPECT image concordance between the 2 agents were examined. Exact categorical agreement in the extent and severity of reversible perfusion defects ranged from 79% to 87%, with kappa values from 0.69 to 0.85, indicating very good to excellent agreement between Binodenoson and adenosine. The risk of any safety event/side effect was significantly lower with any dose of Binodenoson than with adenosine (P< or =0.01) because of a dose-related reduction in subjective side effects, as objective events were infrequent. There was a reduction in the severity of chest pain, dyspnea, and flushing in all Binodenoson doses compared with adenosine (P<0.01), and the magnitude of severity reduction was dose-related. Conclusions: The selective adenosine A2A receptor agonist Binodenoson results in an extent and severity of reversible perfusion defects on SPECT imaging similar to nonselective adenosine receptor stimulation, accompanied by a dose-related reduction in the incidence and severity of side effects.